From the beginning of the nineties in the medical literature lots of studies appeared about a molecule patented as lonapalene (drawings, FIG. 1) with a great power against inflammation of the skin Lonapalene (6-chloro-2,3-dimethoxynaphthalendioldiacetate) has a statistically significant reduction in the levels of material similar or identical to the chemoattractant arachidonate 5-lipoxygenase product, leukotriene B4 (Black A. K., LAMP R D., Malled A T., Cunningham F M., Hofbauer M., Greaves M W.; PHARMACOLOGIC AND CLINICAL EFFECTS OF LONAPALENE-RS43-179-A 5-LIPOXYGENASE INHIBITOR IN PSORIASIS; JOURNAL OF INVESTIGATIVE DERMATOLOGY 95(1):50-4, 1990 July) A wide variety of agents have been reported as 5-lipooxygenase inhibitors. The majority of the series appear to be lipophilic reducing agents, including phenols, partially saturated.
Aromatics and compounds containing heteroatom-hetero atom bonds are the-same. Many of these are not selective 5-LO inhibitors.
In vivo sistemic activity for many of these has been in general, disappointing, probably because of poor bioavailability caused by lipophilicity and metabolic instability (oxidation and conjugation of phenolic compounds). However, topically a number of agents have shown promise for skin inflammation, and best of all, lonapalene; (Batt D G., 5-LIPOXYGENASE INHIBITORS AND THEIR ANTI-INFLAMMATORY ACTIVITIES, PROGRESS IN MEDICINAL CHEMISTRY, 29:1-63, 1992).
Unfortunately, the clinical utilisation of lonapalene wasn't successful, probably because of the remarkable side effects. Lots of attempts have been made to find other topical nonsteroidal antipsoriatic agents analogues of lonapalene, without any success;(Venuti M C., Loe B E., Jones G H., Young G M., TOPICAL NONSTEROIDAL AN TIPSORIATIC AGENTS. 2.2,3-ALKYLIDENEDIOXYNAPHTALENE ANA LOGUES OF LONAPALENE, JOURNAL OF MEDICINAL CHEMISTRY, 31(11):2132-6, 1988 November). (Jones G H., Venuti M C., YOUNG J M., Murthy D V., Loe B E., Simpson R A., Berks A H., Spires D A., Malonej P J., Kruseman M., et al., TOPICAL NON STEROIDAL ANTIPSORIATIC AGENTS. 1.1,2,3,4,-TETRAOXYGENATED NAPHTALENE DERIVATIVES, JOURNAL OF MEDICINAL CHEMISTRY, 29(8):1504-11, 1986 August).